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Regulation of transcription factor suppresses malignant properties of cancer cells with changes in glycosylation

Research Project

Project/Area Number 23590070
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionNagaoka University of Technology

Principal Investigator

SATO Takeshi  長岡技術科学大学, 工学部, 准教授 (30291131)

Co-Investigator(Kenkyū-buntansha) FURUKAWA Kiyoshi  長岡技術科学大学, 工学部, 教授 (10190133)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords転写因子 / がん / 悪性形質 / 腫瘍形成 / 細胞運動 / 糖鎖 / 糖タンパク質 / シグナル伝達
Research Abstract

In this grant, we established the Sp1-knockdown cells from A549 human lung carcinoma cells by RNAi technique, and examined the relationship between protein glycosylation and malignant properties. Lectin blot analysis showed that decreased galactosylation of N-glycans is observed for E-cadherin in the Sp1-knockdown cells. The gene expression level of beta-1,4-GalT I decreased significantly by knockdown of Sp1. Analysis of the promoter region of the human beta-1,4-GalT I gene revealed that the Sp1-binding site are critical for the expression of the gene. Moreover, knockdown of Sp1 resulted in suppression of the tumorigenic potential and migratory activity of A549 cells. Furthermore, the EGF receptor signaling was reduced by knockdown of Sp1. The study indicates that the malignant properties of cancer cells can be suppressed by regulating Sp1 through changes in protein glycosylation, and suggests that Sp1 may be a potential target for cancer therapy.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (32 results)

All 2014 2013 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (20 results) Book (6 results)

  • [Journal Article] Enhanced ex- pression of theβ4-galactosyltrans- ferase 2 gene impairs mammalian tumor growth2014

    • Author(s)
      Tagawa, M., Shirane, K., Yu, L., Sato, T., Furukawa, S., Mizuguchi, H., Kuji, R., Kawamura, K., Takahashi, N., Kato, K., Hayakawa, S., Sawada, S., and Furukawa, K
    • Journal Title

      Cancer Gene Ther

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Gene expression levels ofβ4-galac- tosyltransferase 5 correlate with the tumorigenic potentials of B16-F10 mouse melanoma cells2014

    • Author(s)
      Shirane, K., Kuji, R., Tareyanagi, C., Sato, T., Kobayashi, Y., Furukawa, S., Murata, T., Kubota, S., Ishikawa, Y., Segawa, K., and Furukawa, K
    • Journal Title

      Glycobiology

      Volume: 24 (6) Pages: 532-541

    • Related Report
      2013 Final Research Report
  • [Journal Article] Gene expression levels of β-1,4-galactosyltransferase V correlate with the tumorigenic potentials of B16-F10 mouse melanoma cells2014

    • Author(s)
      Shirane, K., Kuji, R., Tareyanagi, C., Sato, T., Kobayashi, Y., Furukawa, S., Murata, T., Kubota, S., Ishikawa, Y., Segawa, K., and Furukawa, K.
    • Journal Title

      Glycobiology

      Volume: 24 Pages: 532-541

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced expression of the β4-galactosyltransferase 2 gene impairs mammalian tumor growth2014

    • Author(s)
      Tagawa, M., Shirane, K., Yu, L., Sato, T., Furukawa, S., Mizuguchi, H., Kuji, R., Kawamura, K., Takahashi, N., Kato, K., Hayakawa, S., Sawada, S., and Furukawa, K.
    • Journal Title

      Cancer Gene Therapy

      Volume: 21

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ヒトβ-1,4-ガラクトース転移酵素V遺伝子のがん細胞における発現制御2012

    • Author(s)
      佐藤武史、古川清.
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 132 (6) Pages: 691-697

    • NAID

      130001888683

    • Related Report
      2013 Final Research Report
  • [Journal Article] ヒトβ-1,4-ガラクトース転移酵素V遺伝子のがん細胞における発現制御2012

    • Author(s)
      佐藤武史、古川清
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 132 Pages: 691-697

    • NAID

      130001888683

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ヒトβ4-ガラクトース転移酵素1遺伝子のプロモーター領域における転写因子Sp1結合部位の機能解析2013

    • Author(s)
      丹下梨穂、古川清、佐藤武史
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2013-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] A549ヒト肺がん細胞におけるEGF受容体シグナル伝達とβ4-ガラクトース転移酵素1遺伝子の発現2013

    • Author(s)
      佐藤武史、丹下梨穂、古川清
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] A549ヒト肺がん細胞におけるβ4-ガラクトース転移酵素3遺伝子の転写制御機構の解析2013

    • Author(s)
      丹下梨穂、佐藤武史
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト肺癌細胞のN-型糖鎖のガラクトシル化と足場非依存的増殖2013

    • Author(s)
      佐藤武史、古川清
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] A549ヒト肺がん細胞におけるEGF受容体シグナル伝達とβ4-ガラクトース転移酵素1遺伝子の発現2013

    • Author(s)
      佐藤武史、丹下梨穂、古川清
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] A549ヒト肺がん細胞におけるβ4-ガラクトース転移酵素3遺伝子の転写制御機構の解析2013

    • Author(s)
      丹下梨穂、佐藤武史
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒトβ4-ガラクトース転移酵素1遺伝子のプロモーター領域における転写因子Sp1結合部位の機能解析2013

    • Author(s)
      丹下梨穂、古川清、佐藤武史
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 転写因子Sp1の発現抑制によるA549ヒト肺癌細胞のN-型糖鎖のガラクトシル化と足場非依存的増殖の変化2012

    • Author(s)
      佐藤武史、古川清
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      博多
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Sp1の発現制御によるβ-1,4-ガラクトース転移酵素I遺伝子発現の変化2012

    • Author(s)
      佐藤武史、古川清
    • Organizer
      第31回日本糖質学会年会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Sp1のノックダウンによるヒト肺癌細胞のシグナル伝達の変化2012

    • Author(s)
      佐藤武史、古川清
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Sp1の発現制御によるヒト肺癌細胞の糖鎖修飾の変化と細胞運動能の抑制2011

    • Author(s)
      佐藤武史、古川清
    • Organizer
      第5回東北糖鎖研究会
    • Place of Presentation
      仙台
    • Year and Date
      2011-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Knockdown of transcription factor Sp1 suppresses malignant phenotypes of A549 human lung carcinoma cells with changes in N-glycosylation2011

    • Author(s)
      Sato, T
    • Organizer
      Second Joint Austria/Japan Seminar on Comparative and Developmental Glycobiology
    • Place of Presentation
      Vienna
    • Year and Date
      2011-08-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Sp1の発現制御によるヒト肺癌細胞の増殖抑制機構の解明2011

    • Author(s)
      佐藤武史、古川清
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Changes in N-glycosylation and migration of A549 human lung carcinoma cells by knockdown of transcription factor Sp12011

    • Author(s)
      Sato, T., and Furukawa, K
    • Organizer
      21st International Symposium on Glycoconjugates
    • Place of Presentation
      Vienna
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Sp1の発現制御によるN-型糖鎖修飾の変化と細胞運動能の低下2011

    • Author(s)
      佐藤武史、古川清
    • Organizer
      第30回日本糖質学会年会
    • Place of Presentation
      長岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 転写因子Sp1の発現制御によるβ-1,4-ガラクトース転移酵素I遺伝子発現の変化

    • Author(s)
      佐藤 武史
    • Organizer
      第31回日本糖質学会年会
    • Place of Presentation
      鹿児島市民文化ホール(鹿児島県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 転写因子Sp1の発現抑制によるA549ヒト肺癌細胞のN-型糖鎖のガラクトシル化と足場非依存的増殖の変化

    • Author(s)
      佐藤 武史
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場、マリンメッセ福岡(福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト肺癌細胞のN-型糖鎖のガラクトシル化と足場非依存的増殖

    • Author(s)
      佐藤 武史
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 転写因子Sp1の発現制御によるヒト肺癌細胞の糖鎖修飾の変化と細胞運動能の抑制

    • Author(s)
      佐藤 武史
    • Organizer
      第5回東北糖鎖研究会
    • Place of Presentation
      東北大学(宮城県)
    • Related Report
      2011 Research-status Report
  • [Presentation] 転写因子Sp1の発現制御によるヒト肺癌細胞の増殖機構の解明

    • Author(s)
      佐藤 武史
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2011 Research-status Report
  • [Book] Lectin-probed western blot analysis"in "Lectins/Methods in Molecular Bio- logy"2014

    • Author(s)
      Sato, T (Hirabayashi, J. ed)
    • Publisher
      Humana Press(in press)
    • Related Report
      2013 Final Research Report
  • [Book] Expression and transcriptional re- gulation ofβ4-galactosyltransferase genes in cancer. in"Glycoscience : Biology and Medicine"2014

    • Author(s)
      Sato, T., and Furukawa, K (Taniguchi, N. et al. eds)
    • Publisher
      Springer(in press)
    • Related Report
      2013 Final Research Report
  • [Book] UDP-Gal :β-N-Acetylgluco- samineβ4-Galactosyltransferases (β4GalT2,β4GalT3, andβ4GalT4), UDP-Gal : Glucosylceramideβ4-Galac- tosyltransferases (β4GalT5 andβ4GalT6), and UDP-Gal : Xylosylproteinβ4-Galactosyltransferase (β4GalT7, galactosyltransferase I) in Handbook of Glycosyltransferase and Related Genes2014

    • Author(s)
      Furukawa, K., Clausen, H., and Sato, T (Taniguchi, N. et al. eds)
    • Publisher
      Springer(in press)
    • Related Report
      2013 Final Research Report
  • [Book] Lectins/Methods in Molecular Biology2014

    • Author(s)
      Sato, T.
    • Publisher
      Humana Press
    • Related Report
      2013 Annual Research Report
  • [Book] Glycoscience: Biology and Medicine2014

    • Author(s)
      Sato, T., and Furukawa, K.
    • Publisher
      Springer
    • Related Report
      2013 Annual Research Report
  • [Book] Handbook of Glycosyltransferase and Related Genes2014

    • Author(s)
      Furukawa, K., Clausen, H., and Sato, T.
    • Publisher
      Springer
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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